Peripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner.

Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood-brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile.

Novel insights into mechanisms of inhibition of colonic motility by loperamide.

Background: It is well known that opiates slow gastrointestinal (GI) transit, via suppression of enteric cholinergic neurotransmission throughout the GI tract, particularly the large intestine where constipation is commonly induced. It is not clear whether there is uniform suppression of enteric neurotransmission and colonic motility across the full length of the colon. Here, we investigated whether regional changes in colonic motility occur using the peripherally-restricted mu opioid agonist, loperamide to inhibit colonic motor complexes (CMCs) in isolated mouse colon.

Rebound methaemoglobinaemia secondary to intentional sodium nitrite ingestion.

We report a case of rebounding severe methaemoglobinaemia secondary to sodium nitrite ingestion, despite several administrations of methylene blue. The patient's clinical course was characterised by a series of alternating improvements and deteriorations and proved challenging for treating clinicians. On discussion with poisoning experts, it was hypothesised that a small amount of sodium nitrite remained in the gastrointestinal tract leading to prolonged absorption of the causative agent.

Anxiety-like Behavior in Female Sprague Dawley Rats Associated with Cecal Clostridiales.

The relationship between the microbiota profile and exposure to stress is not well understood. Therefore, we used a rat model of unpredictable chronic mild stress (UCMS) to investigate this relationship. Depressive-like behaviors were measured in Female Sprague Dawley rats using the sucrose preference test and the Porsolt swim test.

A Diet Enriched with HN001 and Milk Fat Globule Membrane Alters the Gut Microbiota and Decreases Amygdala GABA a Receptor Expression in Stress-Sensitive Rats.

Brain signalling pathways involved in subclinical anxiety and depressed mood can be modulated via the gut brain axis (GBA), providing the potential for diet and dietary components to affect mood. We investigated behavioural, physiological and gut microbiome responses to the strain HN001 (LactoB HN001™), which has been shown to reduce postpartum anxiety and depression, and a milk fat globule membrane-enriched product, Lipid 70 (Surestart MFGM Lipid 70), which has been implicated in memory in stress-susceptible Wistar Kyoto rats. We examined behaviour in the open field, elevated plus maze and novel object recognition tests in conjunction with the expression of host genes in neuro-signalling pathways, and we also assessed brain lipidomics.

Slowed gastrointestinal transit is associated with an altered caecal microbiota in an aged rat model.

Gastrointestinal (GI) motility is largely dependent upon activity within the enteric nervous system (ENS) and is an important part of the digestive process. Dysfunction of the ENS can impair GI motility as is seen in the case of constipation where gut transit time is prolonged. Animal models mimicking symptoms of constipation have been developed by way of pharmacological manipulations.

Generation and identification of kokumi compounds and their validation by taste-receptor assay: An example with dry-cured lamb meat.

Kokumi tastants are small γ-glutamyl peptides (GGP) that enhance flavour in foods. We sought to generate GGP from the meat crusts of dry-cured lamb, an underutilised protein resource, identify these using mass spectrometry, and validate their functional activity using a kokumi-calcium sensing receptor (CaSR) assay. The water-soluble extract (WSE) of meat crust was hydrolysed by protease A (PA) and treated with glutaminase (GA).

Microbial signalling in colonic motility.

Sensory nerve endings within the wall of the gastrointestinal (GI) tract may respond to bacterial signalling, providing the basis for key biological processes that underlie intestinal motility and microbial homeostasis. Enteric neurons and smooth muscle cells are well known to express an array of receptors, including G-protein coupled receptors and ligand-gated ion channels, that can sense chemical ligands and other bacterially-derived substances. These include short chain fatty acids, secondary bile acids and lipopolysaccharide.

G Protein-Coupled Receptors in Taste Physiology and Pharmacology.

Heterotrimeric G protein-coupled receptors (GPCRs) comprise the largest receptor family in mammals and are responsible for the regulation of most physiological functions. Besides mediating the sensory modalities of olfaction and vision, GPCRs also transduce signals for three basic taste qualities of sweet, umami (savory taste), and bitter, as well as the flavor sensation kokumi. Taste GPCRs reside in specialised taste receptor cells (TRCs) within taste buds.

Goat milk increases gastric emptying and alters caecal short chain fatty acid profile compared with cow milk in healthy rats.

Goat and cow milk share similar protein and lipid content, yet goat milk forms softer curds during stomach digestion. This has been assumed to hasten gastric emptying (GE) on consumption of goat milk compared with cow milk, although there is no direct evidence for this. We hypothesised that goat milk would increase GE and gastrointestinal transit compared with cow milk and alter short-chain fatty acid (SCFA) profiles.

The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety.

There is emerging evidence that an unhealthy dietary pattern may increase the risk of developing depression or anxiety, whereas a healthy dietary pattern may decrease it. This nascent research suggests that dietary interventions could help prevent, or be an alternative or adjunct therapy for, depression and anxiety. The relation, however, is complex, affected by many confounding variables, and is also likely to be bidirectional, with dietary choices being affected by stress and depression.

Differences in peptide generation following in vitro gastrointestinal digestion of yogurt and milk from cow, sheep and goat.

Fermentation of milk is commonly used throughout the world to produce a variety of foods with different health benefits. We hypothesised that due to differences in physicochemical properties and protein sequences among milk from different species and their fermented yogurt samples, their protein digestion and resulting peptide profiles would differ. Cow, goat and sheep milk and yogurt were compared at designated timepoints throughout in vitro gastric and intestinal digestion for differences in peptide profiles and peptide bioactivities.

Short communication: Processed bovine colostrum milk protein concentrate increases epithelial barrier integrity of Caco-2 cell layers.

Colostrum plays an important role in initiating the development of the intestinal barrier in newborn mammals. Given its bioactivity, there is much interest in the potential use of bovine colostrum to improve human gastrointestinal health throughout the life span. There is evidence that bovine colostrum is effective at improving small intestinal barrier integrity and some indication that it may alter colonic motility.

Metabolome and microbiome profiling of a stress-sensitive rat model of gut-brain axis dysfunction.

Stress negatively impacts gut and brain health. Individual differences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. However, the mechanisms by which these factors influence each other are poorly understood, and there are currently no established robust biomarkers of stress susceptibility.

Alteration in propagating colonic contractions by dairy proteins in isolated rat large intestine.

Gastrointestinal conditions in which the transit of contents is altered may benefit from nutritional approaches to influencing health outcomes. Milk proteins modulate the transit of contents along different regions, suggesting that they have varying effects on neuromuscular function to alter gastrointestinal motility. We tested the hypothesis that bovine whey and casein milk protein hydrolysates could have direct modulatory effects on colonic motility patterns in isolated rat large intestine.

Cryo-EM structures of the pore-forming A subunit from the Yersinia entomophaga ABC toxin.

ABC toxins are pore-forming virulence factors produced by pathogenic bacteria. YenTcA is the pore-forming and membrane binding A subunit of the ABC toxin YenTc, produced by the insect pathogen Yersinia entomophaga. Here we present cryo-EM structures of YenTcA, purified from the native source.

The Effects of Unfermented and Fermented Cow and Sheep Milk on the Gut Microbiota.

A variety of fermented foods have been linked to improved human health, but their impacts on the gut microbiome have not been well characterized. Dairy products are one of the most popular fermented foods and are commonly consumed worldwide. One area we currently lack data on is how the process of fermentation changes the gut microbiota upon digestion.

Bioaccumulation of methylmercury within the marine food web of the outer Bay of Fundy, Gulf of Maine.

Mercury and methylmercury were measured in seawater and biota collected from the outer Bay of Fundy to better document mercury bioaccumulation in a temperate marine food web. The size of an organism, together with δ13 C and δ15 N isotopes, were measured to interpret mercury levels in biota ranging in size from microplankton (25μm) to swordfish, dolphins and whales. Levels of mercury in seawater were no different with depth and not elevated relative to upstream sources.

Meucin-49, a multifunctional scorpion venom peptide with bactericidal synergy with neurotoxins.

Besides key roles in prey capture and predator defense, scorpion venom also functions as internal immune agents protecting the venom gland from infection and external immune agents cleaning saprophytic microbes from their own body surfaces. However, antimicrobials (typically antimicrobial peptides, AMPs) in the venom often exist in low abundance that might exclude their immune role alone, leaving an open question with regard to their in vivo biological function. Here, we report the bactericidal activity of seven peptides isolated from the scorpion Mesobuthus eupeus venom, including one classical α-helical AMP and five ion channel-targeted neurotoxins.

Gastric Emptying and Gastrointestinal Transit Compared among Native and Hydrolyzed Whey and Casein Milk Proteins in an Aged Rat Model.

Little is known about how milk proteins affect gastrointestinal (GI) transit, particularly for the elderly, in whom digestion has been observed to be slowed. We tested the hypothesis that GI transit is faster for whey than for casein and that this effect is accentuated with hydrolysates, similar to soy. Adult male rats (18 months old) were fed native whey or casein, hydrolyzed whey (WPH) or casein (CPH), hydrolyzed blend (HB; 60% whey:40% casein), or hydrolyzed soy for 14 days then treated with loperamide, prucalopride, or vehicle-control for 7 days.

Gastroparesis and lipid metabolism-associated dysbiosis in Wistar-Kyoto rats.

Altered gastric accommodation and intestinal morphology suggest impaired gastrointestinal (GI) transit may occur in the Wistar-Kyoto (WKY) rat strain, as common in stress-associated functional GI disorders. Because changes in GI transit can alter microbiota composition, we investigated whether these are altered in WKY rats compared with the resilient Sprague-Dawley (SD) rats under basal conditions and characterized plasma lipid and metabolite differences. Bead transit was tracked by X-ray imaging to monitor gastric emptying (4 h), small intestine (SI) transit (9 h), and large intestine transit (12 h).

Promotility Action of the Probiotic HN019 Extract Compared with Prucalopride in Isolated Rat Large Intestine.

Attention is increasingly being focussed on probiotics as potential agents to restore or improve gastrointestinal (GI) transit. Determining mechanism of action would support robust health claims. The probiotic bacterium HN019 reduces transit time, but its mechanisms of action and effects on motility patterns are poorly understood.

Influence of Bovine Whey Protein Concentrate and Hydrolysate Preparation Methods on Motility in the Isolated Rat Distal Colon.

Whey protein concentrate (WPC) and hydrolysate (WPH) are protein ingredients used in sports, medical and pediatric formulations. Concentration and hydrolysis methods vary for whey sourced from cheese and casein co-products. The purpose of this research was to investigate the influence of whey processing methods on in vitro gastrointestinal (GI) health indicators for colonic motility, epithelial barrier integrity and immune modulation.

Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility.

Background: Dysmotility in the gastrointestinal (GI) tract often leads to impaired transit of luminal contents leading to symptoms of diarrhea or constipation. The aim of this research was to develop a technique using high resolution X-ray imaging to study pharmacologically induced aged rat models of chronic GI dysmotility that mimic accelerated transit (diarrhea) or constipation. The 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist prucalopride was used to accelerate transit, and the opioid agonist loperamide was used to delay transit.